P14.18 Expression and Clinical Significance of CMTM6 in Non-Small Cell Lung Cancer

Abstract

Lung cancer is one of the most serious malignancies, which bearing high estimated new cancer cases and deaths. Although death rate of lung cancer have reduced over the past decade in USA, it still caused more deaths than breast, prostate, colorectal and brain cancers combined. Similarly, the lung cancer situation in China is not optimistic. Nowadays, many drugs against NSCLC have been approved and applicated in clinical, such as PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab). However, there are only 15%-20% of patients can respond to this therapy. For a better understanding and treatment of NSCLC, it is important to explore more and better diagnostic and prognostic biomarkers. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing protein 6 (CMTM6) is a widely expressed protein. In 2017, two independent researches published on Nature reported the biological function of CMTM6 in tumor immunity. As a critical regulator of PD-L1 protein in cancer cells, CMTM6 can bind to PD-L1 and prevent PD-L1 from being targeted for lysosome-mediated degradation, resulting in enhanced inhibitory effect on immune system and successful escape of immune surveillance.All of research mentioned above have been done at the cellular and genetic levels, and it is not entirely clear the expression of CMTM6 in various cancers, such as non-small cell lung cancer. In view of the relationship between CMTM6 and PD-L1 and the critical role of PD-L1 in the immunotherapy of NSCLC, we evaluated the expression and clinical significance of CMTM6 in NSCLC in this study. Firstly, the 109 NSCLC patients’ tissue samples were collected from affiliated hospital of zunyi medical university. Then the expression of CMTM6 in NSCLC patients’ tissue samples and its correlation with prognosis were explored by immunohistochemistry (IHC). Finally, the relationship between CMTM6 expression and clinical characteristics of NSCLC patients were evaluated as well as the survival of NSCLC patients. 109 patients who were diagnosed with NSCLC and underwent surgical resection[何1] were included in this retrospective study. The expression of CMTM6 in NSCLC patients’ tissue samples were measured by immunohistochemistry and the staining intensity were assessed by the multiplication of staining intensity and staining proportion: score ≤ 5 was considered low CMTM6 expression and score > 5 belong to high CMTM6 expression. Sixty out 109 cases (55.05%) had high CMTM6 expression in this study. The Chi-square test showed that the expression of CMTM6 in NSCLC was significantly related with smoking (p = 0.017) and differentiation (p = 0.029). The Kaplan-Meier analysis suggested that the high[何1] expression of CMTM6 was associated with better prognosis of NSCLC patients. The univariate analysis revealed that high CMTM6 expression in NSCLC patients’ tumor tissues was correlated with pathological differentiation (p = 0.001), metastasis (p = 0.009), LNM (p = 0.007) and T stage (p = 0.042). In addition, multivariate analysis indicated that high CMTM6 expression was an independent prognostic factor for NSCLC patients (p = 0.002). The tumor tissue CMTM6 expression may have the potential to be a biomarker assisting in disease monitoring and prognosis in NSCLC.